| Title: |
Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties |
| Authors: |
Li, Min; Ciu, Jing-Rong; Ye, Ying; Min, Ji-Mei; Zhang, Li-He; Wang, Kui; Gares, Michèle; Cros, Jean; Wright, Michel; Leung-Tack, Jeanne |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2002 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
MOLECULAR EPIDEMIOLOGY |
| Description: |
Ajoene, a garlic stable oil-soluble sulfur rich compound was generally isolated as a mixture of two isomers [( E, Z )-4,5,9-trithiadodeca-1,6,11-triene-9-oxide]. It has been described essentially as a potent inhibitor of platelet aggregation in vitro and in vivo . The antiproliferative effects of ajoene and experiments using a single isomer had received little attention. The present study aims at defining the antitumor activities of cis - Z -ajoene in vitro and in vivo. Antiproliferative activity of Z -ajoene was demonstrated against a panel of human tumor cell lines with IC 50 values varying from 5.2 mM to 26.1 mM and at a lower extent in normal marsupial kidney cells (PtK2). Meanwhile, Z -ajoene arrested HL60 cells in G 2 /M phase of cell cycle in a dose and time-dependent way. In PtK2 cells, exposure to 20 μM Z -ajoene for 6 h induced a complete disassembly of the microtubule network, that was associated with an increased number of cells blocked in early mitotic stages. An IC 50 for microtubule disassembly of 1 μM was determined by a fully automated microplate-based multi-detection reader. In vitro , a reversible inhibition of the microtubule protein assembly was observed with an IC 50 of 25 μM Z -ajoene. In vivo, Z -ajoene inhibited tumor growth by 38% and 42% in mice grafted with sarcoma 180 and hepatocarcinoma 22, respectively. For the first time, Z -ajoene was shown to be a potent inhibitor of tumor cell growth both in vitro and in vivo . The microtubule cytoskeleton appeared to be one of the Z -ajoene targets, but the mechanisms by which Z -ajoene interacted with microtubule appeared different from those of other microtubule poisons such as those of the Vinca alkaloids family. The ability of Z -ajoene to preferentially suppress the growth of neoplastic cells could provide a new approach in tumor therapy. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://carcin.oxfordjournals.org/cgi/content/short/23/4/573; http://dx.doi.org/10.1093/carcin/23.4.573 |
| DOI: |
10.1093/carcin/23.4.573 |
| Availability: |
http://carcin.oxfordjournals.org/cgi/content/short/23/4/573; https://doi.org/10.1093/carcin/23.4.573 |
| Rights: |
Copyright (C) 2002, Oxford University Press |
| Accession Number: |
edsbas.82EA5DA1 |
| Database: |
BASE |